School/Research organisations

Abstract

Background: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin.Methods: All grade 3 & 4 adverse events (AEs) and their relationship to
treatment for patients who had taken at least one dose of therapy in the
REMoxTB clinical trial were recorded. Univariable logistic regression
was used to test the relationship of baseline characteristics to the
incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10)
were incorporated into a multivariable model. The timing of AEs during
therapy was analysed in standard therapy and the experimental arms.
Logistic regression was used to investigate the relationship between AEs
(total and related-only) and microbiological cure on treatment.Results: In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1
related AEs with 80 of the total 113 related events (70.8%) occurring in
the intensive phase of treatment. Both four-month experimental arms
(“isoniazid arm” with moxifloxacin substituted for ethambutol &
“ethambutol arm” with moxifloxacin substituted for isoniazid) had a
lower total of related grade 3 & 4 AEs than standard therapy (63
& 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91–1.83) and
HIV-positive status (adjOR 3.33, 95% CI 1.55–7.14) were significantly
associated with experiencing ≥1 related AE (p < 0.05)
on standard therapy. The most common adverse events on standard therapy
related to hepatobiliary, musculoskeletal and metabolic disorders.
Patients who experienced ≥1 related AE were more likely to fail
treatment or relapse (adjOR 3.11, 95% CI 1.59–6.10, p < 0.001).Conclusions: Most AEs considered related to standard therapy occurred in the
intensive phase of treatment with female patients and HIV-positive
patients demonstrating a significantly higher risk of AEs during
treatment. Almost a tenth of standard therapy patients had a significant
side effect, whereas both experimental arms recorded a lower incidence
of toxicity. That patients with one or more AE are more likely to fail
treatment suggests that treatment outcomes could be improved by
identifying such patients through targeted monitoring.